Inken Wierstra, Jrgen Alves
The central domain of transcription factor FOXM1c directly interacts with itself in vivo and switches from an essential to an inhibitory domain depending on the FOXM1c binding site
We have previously shown that FOXM1c can transactivate its target genes by two different
mechanisms depending on the FOXM1c binding site. In the present study, by introducing a
small 46-amino-acid-deletion we confirm that the central domain of FOXM1c is essentially
required for transactivation of the minimal c-myc P1 and P2 promoters via their TATA-boxes
but functions as an inhibitory domain on conventional FOXM1c binding sites. Thus, distinct
FOXM1c binding sites determine opposite functions of the central domain suggesting an
allosteric control of its conformation by the DNA binding site. This is strongly supported by
the identification of a direct in vivo interaction of the central domain with itself in the present
study. In contrast, the DNA binding domain binds neither to itself nor to any other domain of
FOXM1c. Transrepression by the central domain is unlikely to be achieved by recruitment of
co-repressors but instead seems to be mediated by direct interference with the basal
transcription complex. Direct binding of the central domain to itself should be involved in
transrepression. Finally, FOXM1c transactivates the chicken mim-1 promoter, whose TATAbox
represents a conventional FOXM1c binding site, so that transactivation follows neither of
the two mechanisms but shows an intermediate behaviour.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 2007
Pages: -
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